Saliva is an integral component of oral physiology and critical for the maintenance of oral health. Impaired production and/or secretion of saliva can have a significant impact on speech, taste and swallowing and lead to increased risk of dental caries and oral infection. In patients with head and neck cancer, salivary gland dysfunction is one of the common complications of radiation therapy (RT). Xerostomia (severe dry mouth) is a debilitating side-effect of RT that adversely affects quality of life in these patients. Clinical evaluation of xerostomia involves patient-based or physician-based grading systems that are subjective and prone to error and variability. Conventional sialographic and scintigraphic methods allow for objective evaluation of salivary gland dysfunction but are either invasive or require the use of radioisotopes and are therefore not ideal for longitudinal assessment in patients. Development of a cheap, reliable, and easy to use non-invasive imaging method for salivary gland imaging could therefore be of immense clinical benefit. In this application, we propose to utilize photoacoustic imaging (PAI), a relatively new imaging technique that allows for non-invasive assessment of salivary gland structure and function. Given the relationship between blood flow and saliva production, we hypothesize that PAI-based hemodynamic assessment can serve as a reliable read-out of salivary gland function in vivo. In support of this hypothesis, preliminary studies conducted in our laboratory have shown that PAI can detect changes in salivary gland hemodynamics following gustatory stimulation in vivo. Changes in PAI-based measures of oxygen saturation showed good correlation with power Doppler sonography measures of vascularity. Vascular response to gustatory stimulation was significantly reduced 24 hours following RT suggestive of early radiation-induced vascular injury of salivary glands. Building on these preliminary observations, this application will test the central hypothesis that PAI can be used for non-invasive assessment of salivary gland function and radiation-induced salivary gland injury in vivo. We propose to examine the potential of PAI for salivary gland imaging in small (Aim 1) and large animal (Aim 2) models, conduct a pilot study (Aim 3) in healthy human volunteers and head and neck cancer patients undergoing radiation treatment.